Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan.

The treatment of hypertensive patients with losartan is very common. Despite the reduction in blood pressure, its effects on cardiac contractility and sympathetic autonomic drive are still controversial. In turn, aerobic physical training (APT) also presents an important therapeutic option, providing significant improvements in cardiovascular autonomic control, however little is known about its effects on cardiac contractility, especially when associated with losartan. Therefore, we investigated in spontaneously hypertensive rats (SHR) the effects of losartan and APT on cardiac hemodynamics and functionality, with emphasis on autonomic tonic balance and cardiac contractility. Sixty-four SHR (18 weeks old) were divided into four groups (N = 16): vehicle; vehicle submitted to APT through swimming for 12 weeks; treated with losartan (5 mg·kg-1·d-1) for 12 weeks; and treated with losartan associated with APT. The groups were submitted to cardiac morphological and functional analysis by echocardiography; double blockade of cardiac autonomic receptors with atropine and propranolol; and coronary bed reactivity and left ventricular contractility analyses by the Langendorff technique. APT improved functional parameters and autonomic balance by reducing sympathetic drive and/or increasing vagal drive. In contrast, it promoted a concentric remodeling of the left ventricle (LV). Treatment with losartan reduced sympathetic autonomic drive and cardiac morphological parameters, but there were no significant gains in cardiac functionality and contractility. When combined, the concentric remodeling of the LV to APT was abolished and gains in cardiac functionality and contractility were observed. Our findings suggest that the effects of losartan and APT are complementary and should be applied together in the treatment of hypertension. In spontaneously hypertensive rats, the combination of aerobic physical training with losartan treatment was crucial to greater blood pressure reductions and an increase in left ventricular contractility. Furthermore, losartan treatment prevented the concentric left ventricular remodeling caused by aerobic physical training.

Integrative physiological study of adaptations induced by aerobic physical training in hypertensive hearts.

Aerobic physical training reduces arterial pressure in patients with hypertension owing to integrative systemic adaptations. One of the key factors is the decrease in cardiac sympathetic influence. Thus, we hypothesized that among other causes, cardiac sympathetic influence reduction might be associated with intrinsic cardiac adaptations that provide greater efficiency. Therefore, 14 spontaneously hypertensive rats (SHR group) and 14 normotensive Wistar Kyoto rats (WKY group) were used in this study. Half of the rats in each group were trained to swim for 12 weeks. All animals underwent the following experimental protocols: double blockade of cardiac autonomic receptors with atropine and propranolol; echocardiography; and analysis of coronary bed reactivity and left ventricle contractility using the Langendorff technique. The untrained SHR group had a higher sympathetic tone, cardiac hypertrophy, and reduced ejection fraction compared with the untrained WKY group. In addition, reduced coronary bed reactivity due to increased flow, and less ventricular contractile response to dobutamine and salbutamol administration were observed. The trained SHR group showed fewer differences in echocardiographic parameters as the untrained SHR group. However, the trained SHR group showed a reduction in the cardiac sympathetic influence, greater coronary bed reactivity, and increased left intraventricular pressure. In conclusion, aerobic physical training seems to reduce cardiac sympathetic influence and increase contractile strength in SHR rats, besides the minimal effects on cardiac morphology. This reduction suggests intrinsic cardiac adaptations resulting in beneficial adjustments of coronary bed reactivity associated with greater left ventricular contraction.

Heart Rate Variability and Cardiovascular Fitness: What We Know so Far.

Fluctuation analysis in intervals between heartbeats provides important indices related to autonomic modulation of heart rate variability (HRV). These indices are considered predictors of morbidity and mortality as they are frequently altered in patients with chronic degenerative diseases, especially in those with cardiovascular and metabolic diseases. Similarly, a reduction in HRV is common with aging. In all cases, cardiovascular fitness is often reduced to below the predicted values. In turn, increases in cardiovascular fitness through regular physical exercise, especially aerobic exercise, represent an important therapeutic tool capable of promoting positive adjustments in cardiac autonomic modulation. These adjustments are characterized by reduced sympathetic modulatory influence and/or increased vagal modulatory influence on the heart, increasing the HRV. Therefore, several methodological tools have been used to assess the degree of impairment of autonomic modulation and the therapeutic effects of physical exercise. In contrast, establishment of strict protocols in experimental design is a main challenge in establishing HRV analysis as a robust parameter for evaluating cardiovascular homeostasis. Thus, this review aimed to contribute to the understanding of autonomic modulation of HRV and its relationship with cardiovascular fitness, highlighting the advances made thus far, the applicability of analysis tools, and the confounding factors observed frequently.

Effects of chronic cholinergic stimulation associated with aerobic physical training on cardiac morphofunctional and autonomic parameters in spontaneously hypertensive rats.

We investigated hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations in spontaneously hypertensive rats (SHRs) after aerobic physical training associated with chronic cholinergic stimulation. Fifty-four SHRs were divided into two groups: trained and untrained. Each group was further subdivided into three smaller groups: vehicle, treated with pyridostigmine bromide at 5 mg/kg/day, and treated with pyridostigmine bromide at 15 mg/kg/day. The following protocols were assessed: echocardiography, autonomic double pharmacological blockade, heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS). Physical training and pyridostigmine bromide reduced BP and HR and increased vagal participation in cardiac autonomic tonic balance. The associated responses were then potentialized. Treatment with pyridostigmine bromide increased HRV oscillation of both low frequency (LF: 0.2-0.75 Hz) and high frequency (HF: 0.75-3 Hz). However, the association with physical training attenuated HF oscillations. Additionally, treatment with pyridostigmine bromide also increased LF oscillations of BPV. Both treatment groups promoted morphofunctional adaptations, and associated increased ejection volume, ejection fraction, cardiac output, and cardiac index. In conclusion, the association of pyridostigmine bromide and physical training promoted greater benefits in hemodynamic parameters and increased vagal influence on cardiac autonomic tonic balance. Nonetheless, treatment with pyridostigmine bromide alone seems to negatively affect BPV and the association of treatment negatively influences HRV.